pharmacology

A variety of topics involved with pharmacology, including neuropharmacology, renal pharmacology, human metabolism, intracellular metabolism, and intracellular regulation.

Pharmacology (from Greek φάρμακον, pharmakon, "drug"; and -λογία, -logia) is the study of drug action.^[1] More specifically, it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties, interactions, toxicology, therapy, and medical applications and antipathogenic capabilities. Pharmacology is not synonymous with pharmacy, which is the name used for a profession, though in common usage the two terms are confused at times. Pharmacology deals with how drugs interact within biological systems to affect function. It is the study of drugs, of the body's reaction to drugs, the sources of drugs, their nature, and their properties. In contrast, pharmacy is a medical science concerned with the safe and effective use of medicines.

The origins of clinical pharmacology date back to the Middle Ages in Avicenna's The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas.^[2] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.^[3] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.^[4] The first pharmacology department was set up by Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.^[3]

Early pharmacologists focused on natural substances, mainly plant extracts. Pharmacology developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts.^[5]

Divisions

Pharmacology as a chemical science is practiced by pharmacologists. Subdisciplines include

• clinical pharmacology - the medical field of medication effects on humans
• neuro- and psychopharmacology (effects of medication on behavior and nervous system functioning),
• pharmacogenetics (clinical testing of genetic variation that gives rise to differing response to drugs)
• pharmacogenomics (application of genomic technologies to new drug discovery and further characterization of older drugs)
• pharmacoepidemiology (study of effects of drugs in large numbers of people)
• toxicology study of harmful effects of drugs
• theoretical pharmacology
• posology - how medicines are dosed
• pharmacognosy a branch of pharmacology dealing especially with the composition, use, and development of medicinal substances of biological origin and especially medicinal substances obtained from plants also known as deriving medicines from plants

Scientific background

The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function).

A chemical has, from the pharmacological point-of-view, various properties. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic).

When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in LADME:

• Liberation - disintegration (for solid oral forms {breaking down into smaller particles}), dispersal and dissolution
• Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)?
• Distribution - How does it spread through the organism?
• Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic?
• Excretion - How is the medication eliminated (through the bile, urine, breath, skin)?

Medication is said to have a narrow or wide therapeutic index or therapeutic window. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors.

Medicine development and safety testing

Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration and they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMEA and they enforce standards set by the European Pharmacopoeia.

The metabolic stability and the reactivity of a library of candidate drug compounds have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism; one example of a recent computational method is SPORCalc^[6]. If the chemical structure of a medicinal compound is altered slightly, this could slightly or dramatically alter the medicinal properties of the compound depending on the level of alteration as it relates to the structural composition of the substrate or receptor site on which it exerts its medicinal effect, a concept referred to as the structural activity relationship (SAR). This means that when a useful activity has been identified, chemists will make many similar compounds called analogues, in an attempt to maximize the desired medicinal effect(s) of the compound. This development phase can take anywhere from a few years to a decade or more and is very expensive.^[7]

These new analogues need to be developed. It needs to be determined how safe the medicine is for human consumption, its stability in the human body and the best form for delivery to the desired organ system, like tablet or aerosol. After extensive testing, which can take up to 6 years the new medicine is ready for marketing and selling.^[7]

As a result of the long time required to develop analogues and test a new medicine and the fact that of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, costing millions of dollars. To recoup this outlay pharmaceutical companies may do a number of things:^[7]

• Carefully research the demand for their potential new product before spending an outlay of company funds.^[7]
• Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time.^[7]

Drug legislation and safety

In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements:

1. The drug must be found to be effective against the disease for which it is seeking approval.
2. The drug must meet safety criteria by being subject to extensive animal and controlled human testing.

Gaining FDA approval usually takes several years to attain. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome.^[8]

The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987.

The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.

Education

The study of pharmacology is offered in many universities worldwide.
Again, pharmacology education programs differ from pharmacy programs. Students of pharmacology are trained as researchers, studying the effects of substances in order to better understand the mechanisms which might lead to new drug discoveries for example. Whereas a pharmacy student will eventually work in a pharmacy dispensing medications or some other position focused on the patient, pharmacologist will typically work within a laboratory setting.

Some higher educational institutions combine pharmacology and toxicology into a single program as does Michigan State University. Michigan State University offers PhD training in Pharmacology & Toxicology with an optional Environmental Toxicology specialization. They also offer a Professional Science Masters in Integrative Pharmacology.

See also

Certain safety factor Cosmeceuticals Crude drugs Drug design Drug metabolism Drug Discovery Hit to Lead Enzyme inhibitors Pharmaceutical formulation Herbalism International Union of Basic and Clinical Pharmacology List of abbreviations used in medical prescriptions List of withdrawn drugs

Medicare Part D - the new prescription drug plan in the U.S. Medication Medicinal chemistry Neuropharmacology - The Molecular and Behavior study of Disease and Drugs in the Nervous System Neuropsychopharmacology - The detailed comprehensive study of mind, brain and drugs. Nicholas Culpeper - 17th century English Physician who translated and used 'pharmacological texts'. Pharmaceutical company

Pharmacy and Pharmacology portal Pharmacognosy Pharmacopoeia Pharmacotherapy Pharmakeia Pharmakos Placebo (origins of technical term) Prescription drug Prescription Drug Marketing Act (PDMA) Psychopharmacology - medication for mental conditions Traditional Chinese Medicine

Footnotes

External links

• Pharmaceutical company profiles at NNDB.
• International Conference on Harmonisation.
• US Pharmacopeia.
• International Union of Basic and Clinical Pharmacology.
• IUPHAR Committee on Receptor Nomenclature and Drug Classification.